Extensive Research Description
My main interestis heart and vascular diseases caused by inflammation. Excessive/chronicinflammatory responses (e.g., TNF) and increases in reactive oxygen species(ROS) represent common pathogenic mechanism for atherosclerosis. The vascularcell that primarily limits the inflammatory and atherosclerotic process is thevascular endothelial cells (EC). Inflammation/ROS induces EC dysfunction bydisturbing normal homeostasis, relaxation and survival. These defects in ECfunction are mediated by cytokine/redox-regulated signal transduction and genetranscription. My experiments are designed to dissect signal pathways duringinflammatory responses. We have identified that AIP1 plays important roles inTNF signaling pathways in EC by interacting with ASK1,TRAF2 and RIP1. AIP1'sother functions such as tumor suppression are under investigation.
- Zhang H, He Y, Dai S, Xu Z, Luo Y, Wan T, Luo D, Jones D, Tang S, Chen H, Sessa WC, Min W.(2008)AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. J. Clin. Invest.
- Min W, Lin Y, Tang S, Yu L, Zhang H, Wan T, Luhn T, Fu H, Chen H.(2008) AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor Induced ASK1-JNK Activation. Circulation Research.102(7):840-8
- Luo D, He Y, Zhang H, Luyang Yu, Chen H, Xu Z, Tang S, Urano F, Min M.(2008) AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. J Biol Chem.283(18):11905-12
- Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. (2008). SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death Differ. 15(4):739-50.
- Zhang H , Lin Y, Li J, Pober JS, Min W.(2007) RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for TNF-induced ASK1-JNK/p38 activation. J Biol Chem. 282(20):14788-96.
- Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R, Huang Y, Bernatchez P, Giordano FJ, Shadel G, Sessa WC, Min W. (2007) Endothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions. Am J Pathol. 170(3):1108-20.
- Zhang H, Zhang R, Luo Y, D'Alessio A, Pober JS, Min W.(2004) AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation. J Biol Chem. 279(43), 44955-44965.
- Zhang H, Altman S. (2004) Inhibition of the expression of the human RNase P protein subunits Rpp21, Rpp25, Rpp29 by external guide sequences (EGSs) and siRNA. J Mol Biol. 342(4):1077-83.